Background Palliative systemic treatment in patients with advanced or metastatic esophagogastric cancer may result in improved overall survival and quality of life but can also lead to considerable toxicity. In various cancer types, severe muscle mass depletion (sarcopenia) and poor muscle strength are associated with decreased survival and increased chemotherapy‐related toxicity. The aim of this study is to determine the impact of body composition on survival and chemotherapy toxicity in esophagogastric cancer patients treated with first‐line palliative chemotherapy. Methods A total of 88 patients with advanced esophagogastric cancer treated with standard first‐line palliative systemic therapy consisting of capecitabine and oxaliplatin (CapOx) between January 2010 and February 2017 were included. Skeletal muscle index (SMI), reflecting muscle mass, and skeletal muscle density (SMD), associated with muscle strength, were measured using pre‐treatment of all patients and evaluation computed tomography scans after three treatment cycles of 65 patients and were used to determine sarcopenia and sarcopenic obesity (i.e. sarcopenia and body mass index >25 kg/m 2 ). The associations between body composition (SMI, SMD, sarcopenia, and sarcopenic obesity) and survival and toxicity were assessed using univariable and multivariable Cox and logistic regression analyses, respectively. Results Of 88 patients, 75% was male, and median age was 63 (interquartile range 56–69) years. The majority of patients had an adenocarcinoma (83%). Before start of treatment, 49% of the patients were sarcopenic, and 20% had sarcopenic obesity. Low SMD was observed in 50% of patients. During three cycles CapOx, SMI significantly decreased, with a median decrease of 4% (interquartile range −8.6–−0.4). Median progression‐free and overall survival were 6.9 and 10.1 months. SMI, SMD, sarcopenia, and sarcopenic obesity (both pre‐treatment and after three cycles) were neither associated with progression‐free nor overall survival. Pre‐treatment SMD was independently associated with grade 3–4 toxicity (odds ratio 0.94; 95% confidence interval 0.89–1.00) and sarcopenic obesity with grade 2–4 neuropathy (odds ratio 3.82; 95% confidence interval 1.20–12.18). Conclusions Sarcopenia was not associated with survival or treatment‐related toxicity in advanced esophagogastric cancer patients treated with CapOx. Pre‐treatment sarcopenic obesity was independently associated with the occurrence of grade 2–4 neurotoxicity and skeletal muscle density with grade 3–4 toxicity.

Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of this disease’s etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer’s patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.

Background Objective evaluation of treatment response is the gold standard in ulcerative colitis (UC). In this setting, intestinal ultrasound (IUS) is a non-invasive alternative to endoscopy. Recent studies showed change in IUS parameters after treatment initiation but studies with an endoscopic reference standard are scarce. The aim of this study was to evaluate early change of IUS parameters and determine cut-off values for endoscopic endpoints in UC patients starting anti-inflammatory treatment. Methods In this longitudinal prospective study consecutive patients with moderate-severe UC (baseline endoscopic Mayo score (EMS)≥2) starting an anti-inflammatory treatment were included. Clinical scores, biochemical parameters and IUS parameters were collected at baseline, after 2 (T1), 6 (T2) and 8–26 weeks (T3) around time of the second sigmoidoscopy/colonoscopy. IUS parameters were measured as previously established1. Endoscopic remission (ER) and mucosal healing (MH) were evaluated in the sigmoid and defined as EMS=0 and EMS≤1, respectively. The ultrasonographist and endoscopist were blinded for the outcomes of endoscopy and IUS, respectively. Results 51 consecutive patients were included (Table 1) of whom 31 underwent a second endoscopy (MH: n=15 (45%), ER: n=9 (27%)). Two additional patients underwent colectomy and were considered non-responders. 18 patients did not undergo second endoscopy due to the COVID-19 pandemic (n=2), refusal (n=5), loss to follow-up (n=1) or treatment escalation because of clinical deterioration confirmed by IUS and biomarkers before second endoscopy was performed (n=10). Bowel wall thickness (BWT) was significantly lower from T2 onwards in patients reaching MH (p=0.026) and ER (p=0.002) at T3 (Fig 1). A significant decrease in BWT was already visible at T1 in patients receiving infliximab (p=0.001) or tofacitinib (p=0.007), but not in patients treated with vedolizumab (p=0.11) (Fig 2). Most accurate BWT cut-off values at T3 to determine MH and ER were 3.52 mm (AUROC: 0.95, 95% CI: 0.86–1.00, p<0.0001, sens: 91%, spec: 91%) and 2.98 mm (AUROC: 0.94, 95% CI: 0.85–1.00, p=0.001, sens: 87%, spec: 100%), respectively. Other IUS parameters at T3 did not improve association with MH or ER. IUS parameters at T2 that predict MH and ER are demonstrated in Table 2. Table 1 Fig 1 Fig 2 Table 2 Conclusion BWT and Colour Doppler Signal 6 weeks after start of treatment are associated with and could predict MH and ER. In addition, treatment response patterns at IUS are drug-specific. Furthermore, we have provided accurate BWT cut-off values for endoscopic outcomes. In a point-of-care setting, (early) treatment evaluation with IUS could guide treatment decision in UC in order to optimize treatment response. Reference 1. Bots et al, JCC, 2021

Background Increasing evidence suggests appendectomy as potential alternative treatment in patients with ulcerative colitis (UC), especially in those with histological appendiceal inflammation (AI). Intestinal ultrasound (IUS) is a non-invasive diagnostic modality that detects differences in the appendix between UC patients and healthy controls1. This study aimed to correlate appendiceal IUS and endoscopic findings to histopathological inflammation in resection specimens of UC patients undergoing appendectomy. Methods In this prospective cohort study, appendiceal IUS was performed in UC patients undergoing endoscopy and subsequent appendectomy between 2020 and 2022 in a trial for UC (NCT03912714). Primary outcome was the correlation between an increased maximal cross-sectional diameter (MCD, ≥ 6 mm) and AI in patients with a visible appendix on IUS. Presence of AI was assessed in pathology reports. Patients with fibrosis (F) were excluded from IUS analyses. Secondary outcomes included bowel wall thickness (BWT) on IUS and presence of endoscopic peri-appendiceal red patch (PARP) before appendectomy. Results In total, 32 UC patients who underwent laparoscopic appendectomy in study setting were included (84% female, median age 40 [IQR 27-50] years). The majority of patients demonstrated left sided disease (38%) and a mayo score ≥ 2 (88%) on baseline endoscopy. A median window between ultrasound and appendectomy of 1.2 (0.1-2.1) months was found. A total of eighteen (56%) patients were demonstrated to have AI in the resection specimen, and five (16%) patients demonstrated F. The appendix was visualised on IUS in 25 (78%) UC patients, with no difference in patients with AI (AI: 78%, no AI: 78%, p= 1.0). The overall median MCD and BWT were 5.6 [IQR 4.4-6.6] and 2.2 [1.6-2.5] mm, respectively. Patients with AI demonstrated a numerically higher median MCD (AI: [6.0 [4.2-6.8], no AI: 4.9 [4.4-5.8] mm, p= 0.3). Patients with an increased MCD were more likely to demonstrate pathologic AI, although not significant (OR: 6.0, CI 95%: 0.6-63.7, p=0.1). A minority of patients with AI demonstrated to have an endoscopic PARP: 5/18 (28%). The median MCD of patients with PARP was numerically higher (PARP: 6.0 [IQR 4.4-7.8] vs no PARP: 5.5 [4.0-6.6], p=0.5). Conclusion IUS is a feasible modality for assessment of the appendix. Although significance was not reached, patients with an increased MCD were more likely to demonstrate AI. 1Reijntjes MA, de Voogd FAE, et al. Intestinal ultrasound detects an increased diameter and submucosal layer thickness in the appendix of patients with ulcerative colitis compared to healthy controls - a prospective cohort study. Aliment Pharmacol Ther. 2022 Nov 1.

Background The clinical course of Crohn’s disease (CD) is associated with development of complications including strictures and penetrating lesions such as fistulas and abscesses. Close disease monitoring and optimizing therapy can prevent these complications. Intestinal ultrasound (IUS) is a non-invasive cross-sectional imaging method ideal for frequent assessment of disease activity and intra-abdominal complications. In this meta-analysis we provide an updated assessment of the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, MRI/CT, surgery and pathology. Methods We conducted a literature search in Pubmed/MEDLINE and EMBASE databases from 01-01-1970 up to and including 17-10-2022 for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. A univariate random-effects model was used to calculate the diagnostic test accuracy variables, including the log diagnostic odds ratio and area under the pooled ROC (AUC for SROC). All data were calculated with 95% confidence intervals (CIs). Chi-squared (χ²) test was used to assess study heterogeneity with p < 0.05 indicating significant heterogeneity. Funnel plots were created to assess publication bias. All meta-analysis were performed using the R-package mada. We calculated pooled sensitivity and specificity in Meta-DiSc. Results We identified 1506 studies of which 68 were used for the systematic review. Twenty-three studies with 3863 patients were included in this meta-analysis with an overall moderate to high risk of bias. In total 6 meta-analyses were performed, both for conventional IUS (B-mode) and oral contrast IUS (SICUS) for diagnosing CD-related complications. Pooled overall log diagnostic odds ratio for strictures, fistulas and inflammatory masses by B-mode IUS were 3.56 (2,90-4.21), 3.84 (3.28-4.41) and 3.97 (3.30-4.64) and the AUC were 0.926, 0.896 and 0.960 respectively. Pooled overall diagnostic odds ratio for the diagnosis of strictures, fistulas and inflammatory masses by SICUS were 4.51 (3.28-5.73), 4.80 (3.46-6.14) and 5.46 (3.61-7.30) and the AUC were 0.955, 0.982 and 0.985, respectively. Significant heterogeneity was seen between studies reporting data on diagnosing strictures by B-mode IUS. Conclusion These results indicate that IUS is an accurate tool for the diagnosis of intra-abdominal complications related to CD. IUS as a non-invasive, point-of-care modality is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.